Uterine estrogen sulfotransferase is an enzyme which has been found to be active only in the secretory endometrium of higher mammals. This enzymic activity requires a functional corpora lutea and persists as long as there is a significant level of progesterone in the plasma. Since the estrogen-3-sulfated product does not bind to the estrogen receptor, it is of interest that within porcine and human endometrium the activity of estrogen sulfotransferase appears to be inversely related to the nuclear uptake of estrogen receptor. The objective of the investigation proposed herein is to obtain direct evidence that porcine uterine estrogen sulfotransferase activity is related to the in vivo effect of progesterone carried out via the uterine progesterone receptor. Furthermore, the in vivo effect of a specific inhibitor of estrogen sulfurylation (4-nitro, 3-methoxyestrone) shall be examined. These studies will relate the effect of this non-estrogenic analogue to the estrogen sulfotransferase activity, the nuclear migration of estrogen receptor, the differentiation of the endometrium, and the capacity of a secretory endometrium thus treated to implant the blastocyst. It will be a further aim of this proposal to determine the metabolic fate of 4-nitro, 3-methoxyestrone in gilts. This information will be used to synthesize and test the effectiveness of other estrogen analogues which satisfy known structural requirements of an inhibitor of uterine estrogen sulfotransferase and possibly have improved in vivo activity.